Why is kernicterus still a major cause of death and disability in low-income and middle-income countries?

Abstract

Neonatal jaundice is predominantly a benign condition that affects 60%-80% of newborns worldwide but progresses to potentially harmful severe hyperbilirubinaemia in some. Despite the proven therapeutic benefits of phototherapy for preventing extreme hyperbilirubinaemia, acute bilirubin encephalopathy or kernicterus, several low-income and middle-income countries (LMIC) continue to report high rates of avoidable exchange transfusions, as well as bilirubin-induced mortality and neurodevelopmental disorders. Considering the critical role of appropriate timing in treatment effectiveness, this review set out to examine the contributory factors to the burden of severe hyperbilirubinaemia and kernicterus based on the 'three delays model' described by Thaddeus and Maine in the 91 most economically disadvantaged LMICs with Gross National Income per capita ≤US$6000 and median human development index of 0.525 (IQR: 0.436-0.632). Strategies for addressing these delays are proposed including the need for clinical and public health leadership to curtail the risk and burden of kernicterus in LMICs.

Screening for neonatal deafness in resource-poor countries: challenges and solutions

“…The term "permanent congenital and early-onset hearing loss", or simply "hearing loss", is used more broadly to capture all degrees of hearing loss based on hearing threshold in the better ear averaged over frequencies 0.5, 1, 2, and 4 kHz, classified as: mild (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34), moderate (35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49), moderately severe (50-64 dBHL), severe (65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79), and profound (80)(81)(82)(83)…”

Differences Between Transcutaneous and Serum Bilirubin Measurements in Black African Neonates

“…9 -11 Such discrepancies may compromise the effective management of infants at risk for bilirubin encephalopathy. 12 Limited evidence exists on the pattern and predictors of individual TcB-TSB divergence, especially in settings with predominantly dark-skinned infants or limited access to timely and reliable TSB measurements. [13][14][15] This study, therefore, set out to determine the prevalence and correlates of significant TcB overestimation in a black African population to facilitate optimal decisions for appropriate clinical intervention.…”

The Blockade of NF-κB Activation by a Specific Inhibitory Peptide Has a Strong Neuroprotective Role in a Sprague-Dawley Rat Kernicterus Model

“…Unfortunately, although the level of unconjugated bilirubin (UCB) 3 in the serum can be rapidly reduced by phototherapy and/or exchange transfusion, the UCB that has already entered the nervous system cannot currently be replaced, and the irreversible neurologic damage cannot be prevented. Meanwhile, the limited availability of exchange transfusion and its severe complications remind us that it is critical to explore other effective strategies (2).…”

“…However, neonates with severe unconjugated hyperbilirubinemia may develop kernicterus, particularly those who are premature or have suffered sepsis, hypoxia, etc. Although the incidence rate of kernicterus has been dramatically reduced due to advancements in perinatal medicine, it still occurs throughout the world, particularly in developing countries (1,2). Kernicterus is considered a chronic sequela of acute bilirubin encephalopathy, which may lead to death or lifelong neurological sequelae, such as mental retardation, a developmental motor delay, and epilepsy (3,4).…”